Reference materials for engineered nanoparticle toxicology and metrology

Background: Over the last decade there has been increasing public and private investment in nanotechnology. One of the main outputs of this investment has been the development of new nanomaterials, in particular new nanoparticles (NP), that are already finding their way into a growing range of new consumer and industrial products. However, there is increasing recognition that nanoparticles may pose a risk to human health. Findings from recent toxicology studies have indicated that there are some fundamental properties of nanoparticles which drive their toxicity, and concerns over the safety of NP use by consumers and of release into the environment are significant areas of active research. In the United Kingdom, the Nanotechnology Research Coordination Group (NRCG) was set up by the UK Government to coordinate publicly funded research into the potential risks presented by the products and applications of nanotechnologies. The “Development of testing strategies and methods for human health hazard assessment of nanoparticles” has been identified as an important research objective by the NRCG. Several of the task-forces taking this research forward identified the development of a bank of reference materials for toxicology and metrology as a critical objective. A consortium, led by IOM, was successful in responding to a UK Department of Environment, Food and Rural Affairs (Defra) call for proposals in 2006 on “prioritisation of reference materials for engineered nanoparticle toxicology and metrology”. This report describes the project which resulted (REFNANO) and its outcomes.Methods: The REFNANO project was based on an informed discussion and opinion-gathering activity with representatives from the toxicology, metrology and nanomaterials producer / user communities. This was achieved through representation of the communities on the Project Management Group, the preparation of five topic briefing papers designed to inform discussion at two by-invitation workshops attended by key opinion-leaders in the field, and consultation with other internationally-recognised reference material initiatives.Project Outputs: Based on the discussions and recommendations arising from the two workshops, we have developed a series of outputs from the project. These outputs include: • a rationale and set of criteria for the selection of priority reference/test materials which give precedence to: o industrial nanomaterials produced in large volume; o materials which can be used in hypothesis testing; o materials which can be used for distributed analysis. • a list of eight high priority reference/test materials or types to meet the needs of toxicology and metrology: o carbon black o TiO2 o ZnO o Polystyrene o SWCNT & MWCNT o Ag o Other key metals & metal oxides (e.g. Cu, Ni, Fe, Zn and their oxides) o Combustion-derived NPs.• a further eight lower priority materials to meet the needs of toxicology and metrology; • information relating to the quantities of materials needed and the matrix in which they are present; • a minimum set of six characteristics to be determined for the reference/test materials: o Aerodynamic equivalent diameter o Absolute length o Specific surface area o Number of particles per unit mass o Concentration of bulk and/or surface contaminants o Polymorphic composition • a further ten lower priority parameters for characterisation; • the appropriateness and availability of characterisation methods; • a proposed development schedule for nanoparticle reference materials. Conclusions and future requirements The REFNANO project sought to provide a priority list of candidates for inclusion in a set of reference materials to support measurement, toxicology and risk assessment of engineered nanoparticles in the UK. Consensus has been reached between the toxicology and metrology communities on the rationale for reference materials, a list of priority candidates, their selection criteria and the suitability of existing instrumental techniques for characterisation. The prioritised candidates are toxicologically and industrially relevant at the nano-scale and focus on materials produced and used in the UK. The REFNANO project has identified a series of requirements for the further development and promulgation of reference materials for nanoparticles. These requirements have been grouped according to the following themes: • Existing reference & test materials; • New reference & test materials; • Measurement techniques; • Guidance; • Strategic developments. These recommendations and proposed requirements are offered for consideration by other initiatives considering the development of reference materials, including on-going UK Government, OECD and international projects.